There is a resurgence of interest in the production of new therapeutic agents using botanical sources. Genetically engineered plants can now be used to produce pharmacologically active proteins, including mammalian antibodies, blood product substitutes, vaccines, hormones, cytokines, and a variety of other therapeutic agents. Plant production of pharmaceuticals holds great potential, and may become an important production system for a variety of new biopharmaceutical products such as vaccines.
Current influenza vaccines for example are produced in fertilized eggs, which have to be infected and incubated for an extended period of time before the virus can be harvested and purified using an appropriate production system. Vaccine production in insect or mammalian cells also requires an incubation period necessary for the cells to secrete sufficient amounts of virus. When combined with the adaptation that must be made of the target virus (either as an attenuated virus or as subunit viruses) before being introducible into any of those systems, current production methods of candidate vaccines in response to an emerging threat are taking a long time, in addition of having high costs associated with the cells culture or eggs incubation.
Plants are potentially a low cost and contamination safe factory for the production of recombinant pharmaceutical proteins. Most of the recombinant proteins produced in plants are indistinguishable from their mammalian counterparts, as far as the amino acid sequence, conformation and biological activity. Traditionally, proteins have been produced using complex production systems such as cell culture, yeast, bacteria or eggs. However, the ability to produce proteins in plants has several major advantages. Plants are uniquely capable of efficient protein expression of different complexity levels and glycosylation patterns at high yields and low costs
Limitations to the application of genetically engineered plants often come from the inability of transgenic organisms to accumulate adequate amounts of the recombinant product, as a result of low transcription rates, improper splicing of the messenger, instability of the foreign mRNA, poor translation rates, hyper-susceptibility of the recombinant protein to the action of endogenous proteases or hyper-susceptibility of the recombinant organism to the foreign protein which result in improper and limited growth or in the worst cases, in strong deleterious effects to the host organism. Inadequacy of production level has a direct impact on the development of applications when profit margins are narrow, or when treatment and/or disposal of residual matter causes bio-safety or environmental problems. Improvement of the accumulation level of the desired recombinant product thus appears to be one critical factor that warrants commercialization of many applications of molecular farming.
Plant-based vaccine manufacturing systems represent a viable alternative to the traditional vaccine development processes, and may provide a more efficient long-term solution to a number of the problems with exist with traditional egg-based or cell-based vaccine production. Plants are cost-effective protein producers, and therefore their use for producing proteins for use in commercial applications, such as but not limited to vaccine development, provides a realistic alternative to more traditional processes used to develop and produce such proteins and/or vaccines. Other uses of such plant-produced proteins include for enzymes for industrial processes, therapeutic antibodies, etc.
The use of Virus-Like Particles (VLPs) is emerging as a technology which has been found well suited for being produced using such plant-based vaccine manufacturing techniques. VLPs generally comprise lipid or protein shells studded with proteins or protein portions, which can be specific to a given disease intended to be targeted by a vaccine. VLPs are thus intended to “look” like a target virus, thereby allowing them to be identified by the immune system of a patient and providing immunity towards that target virus. However because they lack the core genetic material of the actual virus, VLPs are non-infectious and thus cannot replicate. The use of plants for the purposes of producing such VLPs and/or other proteins has been found to be more efficient than certain previously used production processes involving cell cultures, yeast, bacteria, etc., which are typically much more complex and therefore costly.
However, certain challenges nonetheless remain with the use of plants for the commercial production of VLPs and/or proteins, most particularly because previously used systems for the infiltration and processing of plants remain relatively laborious and cost ineffective. Accordingly, improvements in making plant-based vaccine production more commercially viable still remain, in terms of the efficiency and cost effectiveness of production, the quality control and standardization of the produced vaccine, for example.
Therefore, there is a need for an improved device capable of performing the infiltration of plants in automated processes, such as a high-throughput process of candidate proteins for vaccine development and a standardized process for the production of recombinant proteins.